Metabolomics profile and 10-year atherosclerotic cardiovascular disease (ASCVD) risk score

Hojat Dehghanbanadaki; Salimeh Dodangeh; Peyvand Parhizkar Roudsari; Shaghayegh Hosseinkhani; Pouria Khashayar; Mohammad Noorchenarboo; Negar Rezaei; Arezou Dilmaghani-Marand; Moein Yoosefi; Babak Arjmand; Kazem Khalagi; Niloufar Najjar; Ardeshir Kakaei; Fatemeh Bandarian; Hamid Aghaei Meybodi; Bagher Larijani; Farideh Razi

doi:10.3389/fcvm.2023.1161761

Metabolomics profile and 10-year atherosclerotic cardiovascular disease (ASCVD) risk score

Front Cardiovasc Med. 2023 May 3:10:1161761. doi: 10.3389/fcvm.2023.1161761. eCollection 2023.

Authors

Hojat Dehghanbanadaki^#¹, Salimeh Dodangeh^#¹, Peyvand Parhizkar Roudsari², Shaghayegh Hosseinkhani³, Pouria Khashayar⁴, Mohammad Noorchenarboo⁵, Negar Rezaei⁶, Arezou Dilmaghani-Marand⁶, Moein Yoosefi⁶, Babak Arjmand⁷, Kazem Khalagi^{8

9}, Niloufar Najjar¹⁰, Ardeshir Kakaei⁹, Fatemeh Bandarian¹⁰, Hamid Aghaei Meybodi¹¹, Bagher Larijani¹, Farideh Razi¹⁰

Affiliations

¹ Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
² Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
³ Metabolic Disorders Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
⁴ Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom.
⁵ Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
⁶ Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
⁷ Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran, Iran.
⁸ Obesity and Eating Habits Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
⁹ Osteoporosis Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
¹⁰ Metabolomics and Genomics Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
¹¹ Personalized Medicine Research 10-Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.

^# Contributed equally.

Abstract

Background: The intermediate metabolites associated with the development of atherosclerotic cardiovascular disease (ASCVD) remain largely unknown. Thus, we conducted a large panel of metabolomics profiling to identify the new candidate metabolites that were associated with 10-year ASCVD risk.

Methods: Thirty acylcarnitines and twenty amino acids were measured in the fasting plasma of 1,102 randomly selected individuals using a targeted FIA-MS/MS approach. The 10-year ASCVD risk score was calculated based on 2013 ACC/AHA guidelines. Accordingly, the subjects were stratified into four groups: low-risk (n = 620), borderline-risk (n = 110), intermediate-risk (n = 225), and high-risk (n = 147). 10 factors comprising collinear metabolites were extracted from principal component analysis.

Results: C₄DC, C_8:1, C₁₆OH, citrulline, histidine, alanine, threonine, glycine, glutamine, tryptophan, phenylalanine, glutamic acid, arginine, and aspartic acid were significantly associated with the 10-year ASCVD risk score (p-values ≤ 0.044). The high-risk group had higher odds of factor 1 (12 long-chain acylcarnitines, OR = 1.103), factor 2 (5 medium-chain acylcarnitines, OR = 1.063), factor 3 (methionine, leucine, valine, tryptophan, tyrosine, phenylalanine, OR = 1.074), factor 5 (6 short-chain acylcarnitines, OR = 1.205), factor 6 (5 short-chain acylcarnitines, OR = 1.229), factor 7 (alanine, proline, OR = 1.343), factor 8 (C_18:2OH, glutamic acid, aspartic acid, OR = 1.188), and factor 10 (ornithine, citrulline, OR = 1.570) compared to the low-risk ones; the odds of factor 9 (glycine, serine, threonine, OR = 0.741), however, were lower in the high-risk group. "D-glutamine and D-glutamate metabolism", "phenylalanine, tyrosine, and tryptophan biosynthesis", and "valine, leucine, and isoleucine biosynthesis" were metabolic pathways having the highest association with borderline/intermediate/high ASCVD events, respectively.

Conclusions: Abundant metabolites were found to be associated with ASCVD events in this study. Utilization of this metabolic panel could be a promising strategy for early detection and prevention of ASCVD events.

Keywords: ASCVD; acylcarnitine; amino acids; cardiovascular disease; metabolomics.

© 2023 Dehghanbanadaki, Dodangeh, Parhizkar Roudsari, Hosseinkhani, Khashayar, Noorchenarboo, Rezaei, Dilmaghani-Marand, Yoosefi, Arjmand, Khalagi, Najjar, Kakaei, Bandarian, Aghaei Meybodi, Larijani and Razi.